Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001212929 | SCV001384540 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-08-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant has not been reported in the literature in individuals with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe231Glyfs*26) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. |
All of Us Research Program, |
RCV004010691 | SCV004831717 | pathogenic | Lynch syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | The c.691_694del (p.Phe231Glyfs*26 ) variant in the PMS2 gene is located on the exon 6 and is predicted to cause shift of reading frame that introduces a premature translation termination codon (p.Phe231Glyfs*26), resulting in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic and frameshift/truncating variants located upstream and downstream to this position have been reported in individuals with Lynch syndrome (PMID: 28514183, 25512458, 35223509). The variant is reported in ClinVar (ID: 942855). The variant is absent in the general population database (gnomAD). Therefore, the c.691_694del (p.Phe231Glyfs*26 ) variant of PMS2 has been classified as pathogenic. |